title: Tumor histological subtyping determined by hormone receptors and HER2 status defines different pathological complete response and outcome to dose-dense neoadjuvant chemotherapy in breast cancer patients.
abstract: OBJECTIVE
  To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients.
  
  
  METHODS
  A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-.
  
  
  RESULTS
  pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR.
  
  
  CONCLUSIONS
  HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR-/HER2- tumors that achieved a pCR.
authors.affiliation: Medical Oncology Service, Hospital Universitario Virgen de la Victoria, Campus Teatinos s/n, 29010, Málaga, Spain, asmoncomed@yahoo.es.
authors.forename: A
authors.initials: A
authors.lastname: Sánchez-Muñoz
authors.forename: Y
authors.initials: Y
authors.lastname: Plata-Fernández
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: A
authors.initials: A
authors.lastname: Jaén-Morago
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Navarro
authors.forename: C
authors.initials: C
authors.lastname: de la Torre-Cabrera
authors.forename: C
authors.initials: C
authors.lastname: Ramirez-Tortosa
authors.forename: J
authors.initials: J
authors.lastname: Pascual
authors.forename: E
authors.initials: E
authors.lastname: Alba
authors.forename: P
authors.initials: P
authors.lastname: Sánchez-Rovira
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004317:Doxorubicin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012074:Remission Induction; D015996:Survival Rate; D000068878:Trastuzumab; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D003841:Deoxycytidine; D004317:Doxorubicin; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; D000093542:Gemcitabine